Chlamydia pneumonia (CP), an intracellular gram-negative bacterium, is a significant human pathogen linked with 5-10% of cases of pneumonia, bronchitis, asthma and sinusitis. Infection with CP is wide spread with 50-70% of adults worldwide being seropositive. A substantial body of evidence has linked chronic CP infections with the development and progression of atherosclerosis and coronary heart disease (CHD). In 2002 alone over 55 new publications have indicated a strong association between CP and CHD. A variety of antibiotics have been used for the treatment of CP infections, however CP is difficult to eradicate, and requires long-term antibiotic therapy. Thus, antibiotic resistance and treatment failures are common. Therefore new approaches to the prevention and treatment of chronic CP infections are urgently needed. Since many botanical products have been used for centuries for the treatment of CHD and infections, we are proposing to investigate the specific effects of standardized botanical extracts on the pathogenesis of CP and its chronic sequelae. The primary goal of the project is to test standardized botanical extracts and combinations of extracts for the prevention and treatment of CP infections, and determine their impact on atherosclerotic plaque development. To accomplish these goals, the extracts will be tested in vitro to determine activity against CP, as well mechanistic studies. Only the most active extracts will also be tested in an animal model. Over the two-year period 12 botanical extracts will be evaluated in vitro and six in vivo. Botanical selection was based on prioritization using complex data analysis of the Napralert database and other literature sources. Data from our preliminary work demonstrates that the hypothesis and methods for this project are scientifically sound, as a number of extracts used traditionally for the treatment of CHD have already shown activity against CP in vitro. These extracts have since been standardized (based on the active constituents) to enhance the activity, and are ready for animal testing. This proposal is a multidisiplinary collaboration with the long-term objective of developing safe and effective standardized botanicals for the prevention/treatment of CP infections, with overall impact on the development of atherosclerosis and CHD. Data and active standardized extracts developed during this work will be used as the basis for future clinical trials.